AB0019 REPLICATIVE STUDY OF GWAS-ASSOCIATED CANDIDATE GENE LOCI IN PATIENTS WITH OSTEOARTHRITIS FROM THE BASHKORTOSTAN REPUBLIC
Authors: Anton Tyurin, Daria Shapovalova, Luiza Lukmanova, Rashit Davletshin, Rita Khusainova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Osteoarthritis (OA) is one of the most common joint diseases and a global socially significant problem. Currently, new methods of early diagnosis of the disease are being developed, before the development of destructive processes in various tissues of the joint. The leading role in determining the pathophysiology of OA is given to the identification of genetic and epigenetic mechanisms. <h3>Objectives:</h3> The main goal of the study was replicative analysis of the associations of loci associated with OA according to the data of genome-wide analysis of associations (GWAS) located near the DOT1L, ALDH1A, GNL3, GLT8D1, ASTN2, FILIP1, SENP6, NCOA3, DVWA, CHA11 genes with various localization OA. <h3>Methods:</h3> DNA samples from 410 women were used (mean age 45.45 ± 2.35). Patients with OA was carried out in accordance with the criteria of the American Association of Rheumatology (1995), the debut of the disease before the age of 55 years and radiographic confirmation. For genotyping, PCR-RFLP analysis using KASP<sup>@</sup> technology was used. As a calculation tool, MS Office Excel 2007 (Microsoft), Statistica v.6.2 (StatSoft), SPSS v.13 (SPSS Inc) software packages are used. <h3>Results:</h3> We conducted replicative analysis of the 12 loci that were the most significantly associated with OA in the results of GWAS study, among which rs12982744 and rs2302061 (DOT1L), rs4836732 (ASTN2), rs9350591 (FILIP1 &amp; SENP6), rs6976 (GLT8D1), rs6094710 (NCOA3), rs11177 (GNL3), rs7639618 (DVWA/COL6A4P1), rs3204689 (ALDH1A2), rs11842874 (MCF2L), s6539153 and rs835487 (CHST11). The rs4836732 locus of the ASTN2 gene showed an association of the *C*C genotype with OA in general (χ2 = 5.064, p = 0.024, OR = 2.78; 95% CI (1.11-6.97), with early manifestation of OA (up to 50 years) (χ2 = 5.357, p = 0.004, OR = 5.35; 95% CI 1.53-18.68) and with generalized osteoarthritis (χ2 = 8.071, p = 0.004, OR = 5; 95% CI 1.52-16.35), which is consistent with the results of GWAS. The *T allele of the rs7639618 locus of DVWA gene showed an association with late onset OA (χ2 = 5.21, p = 0.022, OR = 1.88; 95% CI 1.09-3.24). The *T*T genotype (0.676) of the rs835487 locus (CHST11) was associated with OA of the hip (χ2 = 6.284, p = 0.012, OR = 2.57; 95% CI 1.21-5.48), which contradicts the results GWAS, where the allele *G was significantly associated with OA of the hip in European populations. An association of the allele *C (χ2 = 4.558, p = 0.032, OR = 2.04; 95% CI 1.05-3.95) and its homozygous genotype *C*C (0.115) (χ2 = 6.398, p = 0.01, OR = 22.3; 95% CI 1.22-408.21) in rs2302061 locus of the DOT1L gene with knee OA was find. The *T*T genotype of the rs6976 (GLT8D1) was associated with early manifestation of OA (χ2 = 5.213, p = 0.022, OR = 2.58; 95% CI 1.14-4.26). The study of the rs3204689 locus (ALDH1A) revealed an association of the genotype *C*G with the generalized osteoarthritis (χ2 = 6.071, p = 0.013, OR = 2.52; 95% CI 1.19-5.33) and the genotype *C*C turned out to be protective (χ2 = 5.226, p = 0.022, OR = 0.39; 95% CI 0.17-0.89). <h3>Conclusion:</h3> Thus, the replication of GWAS results does not always confirm the associations identified earlier, which may be due to a number of reasons. <h3>Disclosure of Interests:</h3> None declared